ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells¹

Abstract

The ABCA3 gene, of the ABCA subclass of ATPbinding cassette (ABC) transporters, is expressed exclusively in lung. We report here the cloning, molecular characterization, and distribution of human ABCA3 in the lung. Immunoblot analysis using the specific antibody reveals a 150-kDa protein in the crude membrane fraction of human lung. Immunohistochemical analyses of alveoli show that ABCA3 is expressed only in the type II cells expressing surfactant protein A. At the ultrastructural level, ABCA3 immunoreactivity was detected mostly at the limiting membrane of the lamellar bodies. Since members of the ABCA transporter family are known to be involved in transmembrane transport of endogenous lipids, our findings suggest that ABCA3 plays an important role in the formation of pulmonary surfactant in type II cells. ß 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

A novel conserved targeting motif found in ABCA transporters mediates trafficking to early post-Golgi compartments

“…1 ). Both hABCA3 and SP-C are traffi cked to the lamellar body, a highly specialized lysosomal-like organelle of alveolar epithelial cells responsible for regulated secretion of surfactant lipids and proteins ( 21,25,30 ). Lysosomal-like organelles containing proSP-C can be used as a surrogate for traffi cking in A549 cells ( Fig.…”

“…Since hABCA3 and SP-C are each routed to lysosomallike organelles in lung epithelial cells ( 21,25,30 ), the relative signifi cance of individual residues of the LLLWKN motif for proper traffi cking of ABCA transporters was assessed. To accomplish this, scanning alanine mutagenesis of the ABCA3 transporter protein in combination with coexpression of SP-C in A549 cells was performed.…”

The ABCA subfamily—gene and protein structures, functions and associated hereditary diseases

“…ABCA3 was found to be predominantly expressed in alveolar type II cells in the lung [53]. ABCA3-specific antibody staining of lung tissue revealed ring-like structures in the cytosol of the cells, suggesting that the protein is specifically concentrated in the membrane of lamellar bodies [53].…”

“…ABCA3-specific antibody staining of lung tissue revealed ring-like structures in the cytosol of the cells, suggesting that the protein is specifically concentrated in the membrane of lamellar bodies [53]. Lamellar bodies are densely packed lysosome-like structures storing pulmonary surfactant, a mixture of phospholipids and proteins, which reduces the surface tension at the air-liquid interface.…”

The Importance of Surfactant on the Development of Neonatal Pulmonary Diseases

“…47 The transporting protein ABCA3 has been identified in the membrane that limits the lamellar bodies, and it is expressed in the lung epithelial cells. 48 Newborns with a deficiency of this protein develop respiratory failure during the first 24 hours of life that is refractory to the use of surfactant and ventilation. Chest radiography can detect surfactant deficiency, which is revealed by a ground-glass pattern.…”